In a study of estrogen-progestin co-therapy in older women, 30 healthy women 65-75 years of age were treated for 2 years with Premarin and low dose daily Provera with 30 untreated age-matched BLSA women as controls. Rate of bone loss by DEXA, biochemical indices of bone turnover, plasma lipids, body composition by anthropometry and DEXA, vaginal maturation indices, and responses to questionnaires assessing clinical effects were measured. There were significant increases in bone mineral density which correlated with decreases in biomarkers of bone resorption, as well as significant decreases in total and LDL cholesterol and increases in HDL cholesterol. There were also decreases in depression, anger, and tension as measured by the Profile of Mood Scale and significant decreases in vasomotor symptoms. Frequent adverse effects included breast swelling and tenderness and vaginal spotting. The positive effects on bone, lipids, and affect with minimal adverse effects, suggest that older women should be included in future randomized clinical trials of estrogen use. In a study assessing the longitudinal changes in hormone regulation, bone and mineral metabolism, and glucose and lipid metabolism in healthy women during the menopausal transition, 90 women have completed a total of 465 GCRC outpatient visits. Preliminary analyses suggest that accelerated bone loss may occur prior to the cessation of menses. A sufficient number of outpatient study visits have been performed to warrant longitudinal data analyses comparing the endocrine profiles to the bone biochemistries, bone density measurements, and body composition assessments. These analyses are underway.